Tumor Suppressive Role of the PRELP Gene in Ovarian Clear Cell Carcinoma

Abstract

Ovarian clear cell carcinoma (OCCC) has a poor prognosis, and its therapeutic strategy has not been established. PRELP is a leucine-rich repeat protein in the extracellular matrix of connective tissues. Although PRELP anchors the basement membrane to the connective tissue and is absent in most epithelial cancers, much remains unknown regarding its function as a regulator of ligand-mediated signaling pathways. Here, we obtained sets of differentially expressed genes by PRELP expression using OCCC cell lines. We found that more than 1000 genes were significantly altered by PRELP expression, particularly affecting the expression of a group of genes involved in the PI3K-AKT signaling pathway. Furthermore, we revealed the loss of active histone marks on the loci of the PRELP gene in patients with OCCC and how its forced expression inhibited cell proliferation. These findings suggest that PRELP is not only a molecule anchored in connective tissues but is also a signaling molecule acting in a tumor-suppressive manner. It can serve as the basis for early detection and novel therapeutic approaches for OCCC toward precision medicine.